1. Field of the Invention
The present invention concerns a modified microorganism for the biological preparation of a hydroxy acid comprising culturing a microorganism genetically modified for the bioproduction of an aliphatic hydroxy acid of formula (I), wherein the microorganism comprises a metabolic pathway for the decarboxylation of a hydroxy-2-keto-aliphatic acid metabolite of formula (II) with two enzymes: an enzyme EA1 having a 2-keto acid decarboxylase activity and an enzyme EA2 having a hydroxy aldehyde dehydrogenase activity. The invention also concerns a new method for the fermentative production of an aliphatic hydroxy acid.
2. Description of Related Art
Fermentative production of hydroxy acids by culturing microorganism producing such hydroxy acids are known in the art, including fermentative production with microorganisms genetically modified for an improved production of the hydroxy acids.
Hydroxyacetate, also named glycolic acid, is the first member of the alpha-hydroxy acid family of carboxylic acids. Hydroxyacetate can form copolymers with other alpha-hydroxy acids. The polyester gradually hydrolyzes in aqueous environments at controllable rates. This property makes it useful in biomedical applications such as dissolvable sutures. Production of hydroxyacetate is described, inter alia, in the following document: WO2007/141316.
3-hydroxypropionate, also named 3-hydroxypropanoate or β-hydroxypropionate or 3-HP, is the three carbon member of the alpha-hydroxy acid family of carboxylic acids. Applications of 3-hydroxypropionate include the manufacture of absorbable prosthetic devices and surgical sutures, incorporation into beta-lactams, production of acrylic acid and malonic acid, formation of trifluoromethylated alcohols or diols (such as 1,3-propanediol), polyhydroxyalkanoates, and co-polymers with lactic acid. Production of 3-hydroxypropionate is described, inter alia, in the following documents: WO 2001/16346, WO 2002/42418, WO 2003/062173, WO 2005/118719, WO 2006/022664, JP 2007/082476, WO 2008/027742, WO 2008/091627.
4-hydroxybutyrate, also named γ-hydroxybutyrate or GHB, is the four carbon member of the alpha-hydroxy acid family of carboxylic acids. 4-hydroxybutyrate is a naturally-occurring substance found in the central nervous system. 4-hydroxybutyrate finds some medical applications, to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy, and as a general anesthetic. In addition to its medical uses, there are many commercial uses for 4-hydroxybutyrate, particularly its various polymers and copolymers. Further, there are several related chemicals that are also useful, 4-hydroxybutyraldehyde, lactone gamma butyrolactone (a common solvent and reagent in chemistry), or 1,4-butanediol (used as a solvent and in the manufacture of some types of plastics and fibers). Production of 4-hydroxybutyrate is described, inter alia, in the following documents: WO 2008/115840, WO 2009/061477.
There is an ongoing need for alternative solutions with modified microorganisms, to use various carbon sources and have potential improvement in the production of the hydroxy acids. These technical improvements may be the overall yield of product being produced based on the energy necessary for such production and eventually, the level of impurities and by-products to be specifically controlled for isolation of the product and its marketing and further use. The present invention relates to a new way of producing such hydroxy acids, describing new metabolic pathways from carbon sources to hydroxy acids.